Herpes simplex type 1 (HSV-1) infects about 60% of people in the United States. Most people have either no symptoms or bothersome recurrent sores on the lips or face. Medically serious consequences of HSV-1 include herpes simplex encephalitis (HSE). HSE is usually a recurrent of HSV-1, and occurs in otherwise healthy, immunocompetent people. HSE can be fatal, and typically results in long term brain damage. Herpes simplex keratitis (HSK) is another serious consequence. HSK is part of a spectrum of HSV eye diseases that consume considerable health care resources; HSK can lead to blindness and a need for corneal transplantation. These and other complications are rare on a per-patient basis, but given the high prevalence of HSV-1, overall have a significant health care impact.
There is no HSV-1 vaccine. Recently, mouse labs discovered that immune cells termed HSV-1-specific CD8 T-cells are located at the anatomic site within which HSV-1 resides in a latent, lifelong state. This location is the trigeminal ganglia (TG), which in humans is a kidney-bean sized bit of nerve tissue deep in the bones of the face (left and right side). In the TG, occasional reactivation events take place after which HSV-1 migrates down nerve cells to the skin of the face, the eyes (HSK), or sometimes the lining of the brain (HSE). Mouse studies have shown that an immunologic battle is taking place in the TG, in which highly specific T-cells that recognize discrete, 8-10 amino acid long bits of HSV-1 proteins (epitopes) physically surround HSV-1-infected neurons.
There are no data concerning which of the about 85 HSV-1 genes are actually expressed at the protein level in the TG. Dogma is that new viral particles are assembled somehow in permanently infected neurons in the TG, and then transport down axons to peripheral tissues (skin, eye) or to brain (HSE). It was not previously thought that enough HSV-1 protein was expressed in the right way such that the immune system could recognize this infection in the TG. Nervous system tissue in general is considered “immune silent” and behind a blood-brain barrier, with the body having strong reasons to limit inflammatory damage near irreplaceable neurons.
There remains a need, however, to identify epitopes that can be used for effective vaccines for treatment and/or prevention of HSV infection.